The basic phenomenon of cellular differentiation, both normal and neoplastic, has been the theme of our research endeavors. In these studies, the phenomenon of latency - or the existence of genetic information in a repressed state - has evolved as a major theoretical consideration. The principle objective of the proposed study is to gain insight into the mechanism of tumorigenesis as an expression of genomic derepression. By utilizing our ability to induce tumors in developing frog embryos, we will approach this basic problem on several levels: 1) through the study of early cellular changes indicative of the transformation to neoplasia in the developing kidney cells; 2) through careful examination of the chromosomes of these young tumors and comparison with the chromosomes of normal cells; 3) through a study of the susceptibility of cells to infection and transformation at various stages of development (can vertical transmission and/or the insertion site of an oncogenic agent be localized on the chromosome level in the Lucke tumor system? When is the genetic information which later directs the cell to become neoplastic incorporated into the cell? Are differentiating cells more susceptible to the activation or incorporation of viral DNA than stem cells or already differentiated cells?); and, finally, 4) through a study of the effects of various temperatures on the process of neoplastic transformation in these developing poikilotherms.